Lithium Phenolates Solvated By Tetrahydrofuran And 1,2Dimethoxyethane: Structure Determination Using The Method Of Continuous Variation

摘要

The role of O-Lithiated species has a very strong precedence in literature ranging from well-known reactions like Aldol, Wittig, Brook etc. in academia to their immense uses in pharmaceutical industry. According to recent study by Pfizer, over two decades, 68% of all C-C bond-forming reactions are carbanion based and 44% of them involve enolates, the most common O-Lithiated species. However, despite their prevalence, very little is known about their structure-reactivity relationships due to a lack of understanding stemming from difficulty in characterizing aggregation states in solution. Highly symmetric aggregates coupled with a spectroscopically opaque Li-O bond make this characterization really tough. The method of continuous variation in conjunction with 6Li NMR spectroscopy has been used to characterize lithium phenolates solvated by tetrahydrofuran (THF) and 1,2-dimethoxyethane (DME) with the intention of providing a general solution to this problem. The strategy relies on the formation of ensembles of homo- and heteroaggregated phenolates and plotting them against the mole-fraction of a particular species. In this case, its worth mentioning that phenolates stand on their merits because of their stability, availability, substrate flexibility and aggregate diversity and both the solvents THF and DME offer to examine the influence of mono- and bifunctional ligands on lithium phenolate aggregation. With the help of this method, a very broad range of structurally (both electronically and sterically) different phenolates has been characterized both in THF and DME. While, THF affords tetrameric, dimeric, and monomeric lithium phenolates depending on solvent and substrate concentrations and on the aryl substituents, DME offers five aggregation states ranging from monomer to pentamer, a unique diversity that presumably stems in part from its capacity to serve as either a monodentate or bidentate (chelating) ligand. The occurrence of cyclic trimers and pentameric ladders uniquely in DME suggests that chelation is mandatory. The stabilization by chelation is also supported by DFT computational studies. Not only the aggregation states, the solvation number of a particular aggregation state can also be obtained by fitting the solvent dependent equilibrium of different aggregates to free solvent concentration and this technique has been used to assign solvation numbers of different aggregates in both THF and DME.